OBJECTIVES: 1. Purify a sufficiently large quantity of indolyl-3-alkane alpha-hydroxylase for more extensive antineoplastic and biological studies. 2. Evaluate the effect of different treatment schedules with indolyl-3-alkane alpha-hydroxylase on experimental tumors, alone and in combination with selected tryptophan analogues. Included will be studies employing tryptophan analogues which are degraded by indolyl-3-alkane alpha-hydroxylase; these will be administered to tumor-bearing mice in very high doses, followed by rescue with the enzyme. 3. Continue to test known organisms and soil isolates for production of a therapeutically usable tryptophan-degrading enzyme which is highly specific for L-tryptophan. 4. Study tryptophan metabolism in normal and neoplastic cells, including tumors which are known to be associated with excessive serotonin production. 5. Study the mechanism of antitumor activity of enzyme-mediated tryptophan depletion. 6. Study the uptake and metabolic fate of selected tryptophan analogues with normal and neoplastic cells in the presence and absence of exogenous L-tryptophan. 7. Novel bacterial enzymes have been isolated in our laboratory which deplete plasma histidine and lysine when injected in mice. We will further purify and charactize these enzymes and study their effects on growth of experimental tumors, alone and in combination with analogues. 8. Determine the toxicity of new enzymes in animals. 9. Continue our studies concerned with modification of therapeutic enzymes to improve their therapeutic effectiveness (increase biological half-life, block antigenicity, enhance their distribution outside the vascular space to increace effectiveness on solid tumors).